Human factors can play havoc with quality of task performance in safety-sensitive operations, especially those that run 24-hours, 7-days a week. Research across multiple industries indicates common threads of observable and preventable behaviors that can lead to catastrophic events. Fatigue monotony, overwork and a multitude of other cultural factors and organizational policies can trigger these mental and physical human errors. With recent extensive capital investments in hardware and software to automate continuous operations, the human operating the controls may become complacent and fail to perform as anticipated. Since the chemical plant, maritime aviation and space disasters of the mid-1980＇s, there has been an increased focus on operational procedures. Operational fatigue has been on the National Transportation Safety Board＇s list of Most Wanted Transportation Safety Improvements since the list＇s inception in 1990 [1]. Today, it may be time to re-visit human factors and focus on the human in operational settings in all modes of 24-hour operations The key is to first understand two strategies to prevent shiftwork-related human error. The first strategy is at the organizational level where we can align human resource and safety policies, address aging needs through better shift scheduling, develop work/rest guidelines and design wellness objectives to enhance 24-hour safety performance. The second strategy is at the operational level where employees recognize personal set-ups for human error and take the appropriate measures. These skills are learned through "fatigue counter-measure training." Both strategies will be discussed throughout this article.